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1.
Antibiotics (Basel) ; 13(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38666988

RESUMO

Currently available silver-based antiseptic wound dressings have limited patient effectiveness. There exists a need for wound dressings that behave as comfortable degradable hydrogels with a strong antibiotic potential. The objectives of this project were to investigate the combined use of gallates (either epi gallo catechin gallate (EGCG), Tannic acid, or Quercetin) as both PVA crosslinking agents and as potential synergistic antibiotics in combination with silver nanoparticles. Crosslinking was assessed gravimetrically, silver and gallate release was measured using inductively coupled plasma and HPLC methods, respectively. Synergy was measured using 96-well plate FICI methods and in-gel antibacterial effects were measured using planktonic CFU assays. All gallates crosslinked PVA with optimal extended swelling obtained using EGCG or Quercetin at 14% loadings (100 mg in 500 mg PVA with glycerol). All three gallates were synergistic in combination with silver nanoparticles against both gram-positive and -negative bacteria. In PVA hydrogel films, silver nanoparticles with EGCG or Quercetin more effectively inhibited bacterial growth in CFU counts over 24 h as compared to films containing single agents. These biocompatible natural-product antibiotics, EGCG or Quercetin, may play a dual role of providing stable PVA hydrogel films and a powerful synergistic antibiotic effect in combination with silver nanoparticles.

2.
PLoS One ; 19(3): e0292945, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478570

RESUMO

BACKGROUND: Obesity is a global epidemic affecting all age groups, populations, and income levels across continents, though is known to disproportionately affect socioeconomically disadvantaged populations. The causes of obesity are complex, informed by diet and weight practices, but shaped by social, commercial, and environmental factors and government policy. Consequently, a Whole System Approach (WSA)-which considers the many causes of obesity and shifts the focus away from individuals as points of intervention and puts an emphasis on understanding and improving the system in which people live-is required. This scoping review of reviews aims to: determine how WSAs to diet and healthy weight have been implemented and evaluated nationally and internationally; to determine what models or theories have been used to implement WSAs; describe how WSAs have been evaluated; determine if WSAs are effective; and to identify the contribution of the public and/or service users in the development of WSAs. METHOD: Systematic searches were carried out using CINAHL, Scopus, PsycINFO (ProQuest), the Cochrane Library, and MEDLINE. Included review papers were those that focused on the application of a whole system approach to diet and/or healthy weight, and/or reported the theory/model used to implement or simulate this approach. Databases were searched from 1995 to March 2022 using a combination of text and Medical Subject Headings (MeSH terms). In addition, reference sections of identified articles were examined for additional relevant articles. Covidence software was used to screen titles and abstracts from the electronic databases and resolve conflicts. RESULTS: A total of 20,308 articles were initially retrieved; after duplicate removal 7,690 unique title and abstracts were reviewed, and 110 articles were selected for full text review. On completion of full text review, 8 review articles were included for data extraction. These included: one umbrella review, four systematic reviews, a rapid review, and two literature reviews (one of which was on strategic reports written for government and public health policy). Evaluations of WSA were mainly process evaluations although health outcomes were assessed in some studies. Several conceptual frameworks or mathematical modelling approaches have been applied to WSAs for diet, healthy weight, and obesity to inform their planning or delivery, and to understand/map the associated systems. Common mathematical approaches include agent based or System Dynamic Modelling. Underlying both conceptual and mathematical models is an understanding how the elements of the complex systems impact each other to affect diet, healthy weight, and obesity. WSA implementations have reported some success in positively impacting health outcomes including reducing Body Mass Index, reducing sugary food intake, and increasing physical activity. Public and user involvement in WSA was not widely reported. CONCLUSION: The application of WSA to diet and healthy weight shows promise, yet the research is lagging behind their implementation. Further robust evidence for using WSA to address diet and healthy weight are required, including incorporating process and outcome evaluations (perhaps using established approaches such as Systems Dynamic Modelling). Furthermore, the analysis of epidemiological data alongside longitudinal process and outcome evaluation regarding the implementation of a WSA is required.


Assuntos
Dieta , Obesidade , Humanos , Obesidade/epidemiologia , Exercício Físico , Redução de Peso , Nível de Saúde
3.
J Comp Neurol ; 532(1): e25582, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38289188

RESUMO

Bone and dental tissues are richly innervated by sensory and sympathetic neurons. However, the characterization of the morphology, molecular phenotype, and distribution of nerves that innervate hard tissue has so far mostly been limited to thin histological sections. This approach does not adequately capture dispersed neuronal projections due to the loss of important structural information during three-dimensional (3D) reconstruction. In this study, we modified the immunolabeling-enabled imaging of solvent-cleared organs (iDISCO/iDISCO+) clearing protocol to image high-resolution neuronal structures in whole femurs and mandibles collected from perfused C57Bl/6 mice. Axons and their nerve terminal endings were immunolabeled with antibodies directed against protein gene product 9.5 (pan-neuronal marker), calcitonin gene-related peptide (peptidergic nociceptor marker), or tyrosine hydroxylase (sympathetic neuron marker). Volume imaging was performed using light sheet fluorescence microscopy. We report high-quality immunolabeling of the axons and nerve terminal endings for both sensory and sympathetic neurons that innervate the mouse femur and mandible. Importantly, we are able to follow their projections through full 3D volumes, highlight how extensive their distribution is, and show regional differences in innervation patterns for different parts of each bone (and surrounding tissues). Mapping the distribution of sensory and sympathetic axons, and their nerve terminal endings, in different bony compartments may be important in further elucidating their roles in health and disease.


Assuntos
Axônios , Neurônios , Animais , Camundongos , Microscopia de Fluorescência , Camundongos Endogâmicos C57BL , Terminações Nervosas
4.
Am J Epidemiol ; 193(3): 536-547, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-37939055

RESUMO

The choice of which covariates to adjust for (so-called allowability designation (AD)) in health disparity measurements reflects value judgments about inequitable versus equitable sources of health differences, which is paramount for making inferences about disparity. Yet, many off-the-shelf estimators used in health disparity research are not designed with equity considerations in mind, and they imply different ADs. We demonstrated the practical importance of incorporating equity concerns in disparity measurements through simulations, motivated by the example of reducing racial disparities in hypertension control via interventions on disparities in treatment intensification. Seven causal decomposition estimators, each with a particular AD (with respect to disparities in hypertension control and treatment intensification), were considered to estimate the observed outcome disparity and the reduced/residual disparity under the intervention. We explored the implications for bias of the mismatch between equity concerns and the AD in the estimator under various causal structures (through altering racial differences in covariates or the confounding mechanism). The estimator that correctly reflects equity concerns performed well under all scenarios considered, whereas the other estimators were shown to have the risk of yielding large biases in certain scenarios, depending on the interaction between their ADs and the specific causal structure.


Assuntos
Hipertensão , Julgamento , Humanos , Grupos Raciais
5.
FASEB J ; 38(1): e23380, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38102980

RESUMO

The urinary bladder is supplied by a rich network of sensory and autonomic axons, commonly visualized by immunolabeling for neural markers. This approach demonstrates overall network patterning but is less suited to understanding the structure of individual motor and sensory terminals within these complex plexuses. There is a further limitation visualizing the lightly myelinated (A-delta) class of sensory axons that provides the primary mechanosensory drive for initiation of voiding. Whereas most unmyelinated sensory axons can be revealed by immunolabeling for specific neuropeptides, to date no unique neural marker has been identified to immunohistochemically label myelinated visceral afferents. We aimed to establish a non-surgical method to visualize and map myelinated afferents in the bladder in rats. We found that in rats, the adeno-associated virus (AAV), AAV-PHP.S, which shows a high tropism for the peripheral nervous system, primarily transduced myelinated dorsal root ganglion neurons, enabling us to identify the structure and regional distribution of myelinated (mechanosensory) axon endings within the muscle and lamina propria of the bladder. We further identified the projection of myelinated afferents within the pelvic nerve and lumbosacral spinal cord. A minority of noradrenergic and cholinergic neurons in pelvic ganglia were transduced, enabling visualization and regional mapping of both autonomic and sensory axon endings within the bladder. Our study identified a sparse labeling approach for investigating myelinated sensory and autonomic axon endings within the bladder and provides new insights into the nerve-bladder interface.


Assuntos
Dependovirus , Bexiga Urinária , Ratos , Animais , Dependovirus/genética , Neurônios , Axônios , Medula Espinal/fisiologia , Gânglios Espinais , Neurônios Aferentes
6.
Chest ; 164(6): e178-e179, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38070968
7.
Pharmacy (Basel) ; 11(6)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38133463

RESUMO

The Australian Federal Government's Community Pharmacy Agreement (Agreement), initiated in 1990 and renegotiated every five years with a pharmacy owners' organisation, is the dominant policy directing community pharmacy. We studied the experience with the Agreements of 38 purposively selected individual pharmacists and others of diverse backgrounds, using in-depth, semi-structured interviews. Although perceived to lack transparency in negotiation and operation, as well as paucity of outcome measures, the Agreements have generally supported the viability of community pharmacies and on balance, contributed positively to the public's access to medicines. There were, however, contradictory opinions regarding the impact of the policy's regulation of pharmacy locations, including the suggestion that they provide existing owners with an undue commercial advantage. A reported shortcoming of the Agreements was their impact on pharmacists' abilities to expand their scopes of practice and assist patients to make better use of medicines, in part due to the funding being almost totally focused on supply-related functions. The support for programs such as medication management services was perceived to be limited, and opportunities for diversification in pharmacy practice appeared constrained. Future pharmacy policy developed by the government could be more inclusive of a diverse range of stakeholders, seek to better utilise pharmacists' expertise, and have a greater focus on health outcomes.

8.
Hepatol Commun ; 7(10)2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37695082

RESUMO

BACKGROUND: The use of large-scale data and artificial intelligence (AI) to support complex transplantation decisions is in its infancy. Transplant candidate decision-making, which relies heavily on subjective assessment (ie, high variability), provides a ripe opportunity for AI-based clinical decision support (CDS). However, AI-CDS for transplant applications must consider important concerns regarding fairness (ie, health equity). The objective of this study was to use human-centered design methods to elicit providers' perceptions of AI-CDS for liver transplant listing decisions. METHODS: In this multicenter qualitative study conducted from December 2020 to July 2021, we performed semistructured interviews with 53 multidisciplinary liver transplant providers from 2 transplant centers. We used inductive coding and constant comparison analysis of interview data. RESULTS: Analysis yielded 6 themes important for the design of fair AI-CDS for liver transplant listing decisions: (1) transparency in the creators behind the AI-CDS and their motivations; (2) understanding how the AI-CDS uses data to support recommendations (ie, interpretability); (3) acknowledgment that AI-CDS could mitigate emotions and biases; (4) AI-CDS as a member of the transplant team, not a replacement; (5) identifying patient resource needs; and (6) including the patient's role in the AI-CDS. CONCLUSIONS: Overall, providers interviewed were cautiously optimistic about the potential for AI-CDS to improve clinical and equitable outcomes for patients. These findings can guide multidisciplinary developers in the design and implementation of AI-CDS that deliberately considers health equity.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Transplante de Fígado , Humanos , Inteligência Artificial , Pesquisa Qualitativa
9.
J Am Med Dir Assoc ; 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37739348

RESUMO

OBJECTIVES: This study aimed to assess the distribution of racial disparities in influenza vaccination between White and Black short-stay and long-stay nursing home residents among states and hospital referral regions (HRRs). DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: We included short-stay and long-stay older adults residing in US nursing homes during influenza seasons between 2011 and 2018. Included residents were aged ≥65 years and enrolled in Traditional Medicare. Analyses were conducted using resident-seasons, whereby residents could contribute to one or more influenza seasons if they resided in a nursing home across multiple seasons. METHODS: Our comparison of interest was marginalized vs privileged racial group membership measured as Black vs White race. We obtained influenza vaccination documentation from resident Minimum Data Set assessments from October 1 through June 30 of a particular influenza season. Nonparametric g-formula was used to estimate age- and sex-standardized disparities in vaccination, measured as the percentage point (pp) difference in the proportions of individuals vaccinated between Black and White nursing home residents within states and HRRs. RESULTS: The study included 7,807,187 short-stay resident-seasons (89.7% White and 10.3% Black) in 14,889 nursing homes and 7,308,111 long-stay resident-seasons (86.7% White and 13.3% Black) in 14,885 nursing homes. Among states, the median age- and sex-standardized disparity between Black and White residents was 10.1 percentage points (pps) among short-stay residents and 5.3 pps among long-stay residents across seasons. Among HRRs, the median disparity was 8.6 pps among short-stay residents and 5.0 pps among long-stay residents across seasons. CONCLUSIONS AND IMPLICATIONS: Our analysis revealed that the magnitudes of vaccination disparities varied substantially across states and HRRs, from no disparity in vaccination to disparities in excess of 25 pps. Local interventions and policies should be targeted to high-disparity geographic areas to increase vaccine uptake and promote health equity.

10.
Antibiotics (Basel) ; 12(9)2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37760711

RESUMO

Chlorhexidine is the most commonly used anti-infective drug in dentistry. To treat infected void areas, a drug-loaded material that swells to fill the void and releases the drug slowly is needed. This study investigated the encapsulation and release of chlorhexidine from cellulose acetate nanofibers for use as an antibacterial treatment for dental bacterial infections by oral bacteria Streptococcus mutans and Enterococcus faecalis. This study used a commercial electrospinning machine to finely control the manufacture of thin, flexible, chlorhexidine-loaded cellulose acetate nanofiber mats with very-small-diameter fibers (measured using SEM). Water absorption was measured gravimetrically, drug release was analyzed by absorbance at 254 nm, and antibiotic effects were measured by halo analysis in agar. Slow electrospinning at lower voltage (14 kV), short target distance (14 cm), slow traverse and rotation, and syringe injection speeds with controlled humidity and temperature allowed for the manufacture of strong, thin films with evenly cross-meshed, uniform low-diameter nanofibers (640 nm) that were flexible and absorbed over 600% in water. Chlorhexidine was encapsulated efficiently and released in a controlled manner. All formulations killed both bacteria and may be used to fill infected voids by swelling for intimate contact with surfaces and hold the drug in the swollen matrix for effective bacterial killing in dental settings.

12.
J Pharm Policy Pract ; 16(1): 71, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37308959

RESUMO

BACKGROUND: A series of Community Pharmacy Agreements (Agreements) between the Federal government and a pharmacy-owners' body, the Pharmacy Guild of Australia (PGA) have been influential policy in Australian community pharmacy (CP) since 1990. While ostensibly to support the public's access and use of medicines, the core elements of the Agreements have been remuneration for dispensing and rules that limit the establishment of new pharmacies. Criticism has focused on the self-interest of pharmacy owners, the exclusion of other pharmacy stakeholders from the Agreement negotiations, the lack of transparency, and the impact on competition. The objective of this paper is to determine the true nature of the policy by examining the evolution of the CPA from a policy theory perspective. METHODS: A qualitative evaluation of all seven Agreement documents and their impact was undertaken using policy theories including a linear policy development model, Multiple Streams Framework, Incremental Theory, the Advocacy Coalition Framework, the Theory of Economic Regulation, the Punctuated Equilibrium Framework, and Elite Theory. The Agreements were evaluated using four lenses: their objectives, evidentiary base, stakeholders and beneficiaries. RESULTS: The PGA has acted as an elite organisation with long-standing influence on the policy's development and implementation. Notable has been the failure of other pharmacy stakeholders to establish broad-based advocacy coalitions in order to influence the Agreements. The incremental changes negotiated every 5 years to the core elements of the Agreements have supported the publics' access to medication, provided stability for the government, and security for existing pharmacy owners. Their impact on the evolution of pharmacists' scope of practice and through that, on the public's safe and appropriate use of medication, has been less clear. CONCLUSIONS: The Agreements can be characterised predominantly as industry policy benefiting pharmacy owners, rather than health policy. An emerging issue is whether incremental change will continue to be an adequate policy response to the social, political, and technological changes that are affecting health care, or whether policy disruption is likely to arise.

13.
Sci Data ; 10(1): 335, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37264011

RESUMO

Despite exponential growth in ecological data availability, broader interoperability amongst datasets is needed to unlock the potential of open access. Our understanding of the interface of demography and functional traits is well-positioned to benefit from such interoperability. Here, we introduce MOSAIC, an open-access trait database that unlocks the demographic potential stored in the COMADRE, COMPADRE, and PADRINO open-access databases. MOSAIC data were digitised and curated through a combination of existing datasets and new trait records sourced from primary literature. In its first release, MOSAIC (v. 1.0.0) includes 14 trait fields for 300 animal and plant species: biomass, height, growth determination, regeneration, sexual dimorphism, mating system, hermaphrodism, sequential hermaphrodism, dispersal capacity, type of dispersal, mode of dispersal, dispersal classes, volancy, and aquatic habitat dependency. MOSAIC includes species-level phylogenies for 1,359 species and population-specific climate data. We identify how database integration can improve our understanding of traits well-quantified in existing repositories and those that are poorly quantified (e.g., growth determination, modularity). MOSAIC highlights emerging challenges associated with standardising databases and demographic measures.


Assuntos
Ecossistema , Plantas , Animais , Clima , Conservação dos Recursos Naturais , Filogenia
14.
Artigo em Inglês | MEDLINE | ID: mdl-37184814

RESUMO

BACKGROUND: Racial disparities in receipt of high-dose influenza vaccine (HDV) have been documented nationally, but whether small-area geographic variation in such disparities exists remains unknown. We assessed the distribution of disparities in HDV receipt between Black and White traditional Medicare beneficiaries vaccinated against influenza within states and hospital referral regions (HRRs). METHODS: We conducted a nationally representative retrospective cohort study of 11,768,724 community-dwelling traditional Medicare beneficiaries vaccinated against influenza during the 2015-2016 influenza season (94.3% White and 5.7% Black). Our comparison was marginalized versus privileged racial group measured as Black versus White race. Vaccination and type of vaccine were obtained from Medicare Carrier and Outpatient files. Differences in the proportions of individuals who received HDV between Black and White beneficiaries within states and HRRs were used to measure age- and sex-standardized disparities in HDV receipt. We restricted to states and HRRs with ≥ 100 beneficiaries per age-sex strata per racial group. RESULTS: We detected a national disparity in HDV receipt of 12.8 percentage points (pps). At the state level, the median standardized HDV receipt disparity was 10.7 pps (minimum, maximum: 2.9, 25.6; n = 30 states). The median standardized HDV receipt disparity among HRRs was 11.6 pps (minimum, maximum: 0.4, 24.7; n = 54 HRRs). CONCLUSION: Black beneficiaries were less likely to receive HDV compared to White beneficiaries in almost every state and HRR in our analysis. The magnitudes of disparities varied substantially across states and HRRs. Local interventions and policies are needed to target geographic areas with the largest disparities to address these inequities.

15.
Artigo em Inglês | MEDLINE | ID: mdl-37052798

RESUMO

The mechanisms underlying racial inequities in uncontrolled hypertension have been limited to individual factors. We investigated racial inequities in uncontrolled hypertension and the explanatory role of economic segregation in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). All 3897 baseline participants with hypertension (2008-2010) were included. Uncontrolled hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg), self-reported race (White/Brown/Black people), and neighborhood economic segregation (low/medium/high) were analyzed cross-sectionally. We used decomposition analysis, which describes how much a disparity would change (disparity reduction; explained portion) and remain (disparity residual; unexplained portion) upon removing racial differences in economic segregation (i.e., if Black people had the distribution of segregation of White people, how much we would expect uncontrolled hypertension to decrease among Black people). Age- and gender-adjusted prevalence of uncontrolled hypertension (39.0%, 52.6%, and 54.2% for White, Brown, and Black participants, respectively) remained higher for Black and Brown vs White participants, regardless of economic segregation. Uncontrolled hypertension showed a dose-response pattern with increasing segregation levels for White but not for Black and Brown participants. After adjusting for age, gender, education, and study center, unexplained portion (disparity residual) of race on uncontrolled hypertension was 18.2% (95% CI 13.4%; 22.9%) for Black vs White participants and 12.6% (8.2%; 17.1%) for Brown vs White participants. However, explained portion (disparity reduction) through economic segregation was - 2.1% (- 5.1%; 1.3%) for Black vs White and 0.5% (- 1.7%; 2.8%) for Brown vs White participants. Although uncontrolled hypertension was greater for Black and Brown vs White people, racial inequities in uncontrolled hypertension were not explained by economic segregation.

16.
Bioengineering (Basel) ; 10(3)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36978688

RESUMO

Low dose methotrexate (MTX) is known to effectively decrease type I collagen production in dermal fibroblasts, while increasing the matrix metalloproteinase-1 (MMP-1) production in vitro. For in vivo use as an antifibrotic agent on wounds, a linear and extended controlled release formulation of MTX is required. The objective of this study was to optimize the fabrication of MTX-loaded polymeric microspheres with such properties, and to test the efficacy for the prevention of fibrosis in vivo. Poly lactic-co-glycolic acid (PLGA), Poly (L-lactic acid) (PLLA) and the diblock copolymer, methoxypolyethylene glycol-block-poly (D, L-lactide) (MePEG-b-PDLLA), were used to fabricate microspheres, which were then characterized in terms of size, drug encapsulation efficiency, and in vitro release profiles. The optimized formulation (PLGA with diblock copolymer) showed high drug encapsulation efficiency (>80%), low burst release (~10%) and a gradual release of MTX. The amphipathic diblock copolymer is known to render the microsphere surface more biocompatible. In vivo, these microspheres were effective in reducing fibrotic tissue which was confirmed by quantitative measurement of type I collagen and α-smooth muscle actin expression, demonstrating that MTX can be efficiently encapsulated in PLGA microspheres to provide a delayed, gradual release in wound beds to reduce fibrosis in vivo.

17.
Clin Transplant ; 37(5): e14938, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36786505

RESUMO

Neighborhood socioeconomic deprivation may have important implications on disparities in liver transplant (LT) evaluation. In this retrospective cohort study, we constructed a novel dataset by linking individual patient-level data with the highly granular Area Deprivation Index (ADI), which is advantageous over other neighborhood measures due to: specificity of Census Block-Group (versus Census Tract, Zip code), scoring, and robust variables. Our cohort included 1377 adults referred to our center for LT evaluation 8/1/2016-12/31/2019. Using modified Poisson regression, we tested for effect measure modification of the association between neighborhood socioeconomic status (nSES) and LT evaluation outcomes (listing, initiating evaluation, and death) by race and ethnicity. Compared to patients with high nSES, those with low nSES were at higher risk of not being listed (aRR = 1.14; 95%CI 1.05-1.22; p < .001), of not initiating evaluation post-referral (aRR = 1.20; 95%CI 1.01-1.42; p = .03) and of dying without initiating evaluation (aRR = 1.55; 95%CI 1.09-2.2; p = .01). While White patients with low nSES had similar rates of listing compared to White patients with high nSES (aRR = 1.06; 95%CI .96-1.17; p = .25), Underrepresented patients from neighborhoods with low nSES incurred 31% higher risk of not being listed compared to Underrepresented patients from neighborhoods with high nSES (aRR = 1.31; 95%CI 1.12-1.5; p < .001). Interventions addressing neighborhood deprivation may not only benefit patients with low nSES but may address racial and ethnic inequities.


Assuntos
Transplante de Fígado , Adulto , Humanos , Estudos Retrospectivos , Classe Social , Etnicidade , Avaliação de Resultados em Cuidados de Saúde
18.
J Biomech ; 149: 111481, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36787674

RESUMO

In the early avian embryo, the developing heart forms when bilateral fields of cardiac progenitor cells, which reside in the lateral plate mesoderm, move toward the embryonic midline, and fuse above the anterior intestinal portal (AIP) to form a straight, muscle-wrapped tube. During this process, the precardiac mesoderm remains in close contact with the underlying endoderm. Previous work has shown that the endoderm around the AIP actively contracts to pull the cardiac progenitors toward the midline. The morphogenetic deformations associated with this endodermal convergence, however, remain unclear, as do the signaling pathways that might regulate this process. Here, we fluorescently labeled populations of endodermal cells in early chicken embryos and tracked their motion during heart tube formation to compute time-varying strains along the anterior endoderm. We then determined how the computed endodermal strain distributions are affected by the pharmacological inhibition of either myosin II or fibroblast growth factor (FGF) signaling. Our data indicate that a mediolateral gradient in endodermal shortening is present around the AIP, as well as substantial convergence and extension movements both anterior and lateral to the AIP. These active endodermal deformations are disrupted if either actomyosin contractility or FGF signaling are inhibited pharmacologically. Taken together, these results demonstrate how active deformations along the anterior endoderm contribute to heart tube formation within the developing embryo.


Assuntos
Galinhas , Endoderma , Animais , Embrião de Galinha , Galinhas/metabolismo , Endoderma/metabolismo , Coração , Morfogênese , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/farmacologia
19.
J Allergy Clin Immunol ; 151(5): 1269-1276, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36740144

RESUMO

BACKGROUND: Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness. OBJECTIVE: Our aim was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab in individuals with moderate-to-severe asthma. METHODS: We emulated a hypothetical randomized trial using electronic health records from a large US-based academic health care system. Participants aged 18 years or older with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/µL were eligible for study inclusion. The study period extended from March 2016 to August 2021. Outcomes included the incidence of asthma-related exacerbations and change in baseline FEV1 value over 12 months of follow-up. RESULTS: In all, 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab met the inclusion criteria. Over 12 months of follow-up, 31 exacerbations occurred over 68 person years (0.46 exacerbations per person year) in the dupilumab group, 63 over 68 person years (0.93 per person year) in the omalizumab group, and 86 over 65 person years (1.32 per person year) in the mepolizumab group (adjusted incidence rate ratios: dupilumab vs mepolizumab, 0.28 [95% CI = 0.09-0.84]; dupilumab vs omalizumab, 0.36 [95% CI = 0.12-1.09]; and omalizumab vs mepolizumab, 0.78 [95% CI = 0.32-1.91]). The differences in the change in FEV1 comparing patients who received the different biologics were as follows: 0.11 L (95% CI = -0.003 to 0.222 L) for dupilumab versus mepolizumab, 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab, and 0.026 L (95% CI -0.083 to 0.140 L) for omalizumab versus mepolizumab. CONCLUSIONS: Among patients with asthma and eosinophil counts of at least 150 cells/µL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV1 value than omalizumab and mepolizumab.


Assuntos
Antiasmáticos , Asma , Humanos , Antiasmáticos/uso terapêutico , Asma/etiologia , Imunoglobulina E/uso terapêutico , Omalizumab/uso terapêutico , Pesquisa Comparativa da Efetividade
20.
Hist Psychol ; 26(1): 1-28, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35901381

RESUMO

Arthur R. Jensen (1923-2012) defended the idea that racial differences in intelligence were biologically based. He based his ideas on what he claimed were sound population genetics and evolutionary biology. Viewing his work through the lenses of those disciplines reveals that his arguments for biological racial differences did not meet the minimum evidentiary requirements needed to show that socially defined races were genetic populations. His evidence was from 19th-century race science and the race science of the Nazi regime. His reliance on such evidence supported Jensen's fears that the country was in danger of collapse because of dysgenic breeding by those of low intelligence. Jensen's well-known associations with scientific racists were not incidental to his scientific work, but central because he cited their work throughout his career. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Racismo , História do Século XX , Melhoramento Vegetal , Inteligência , Evolução Biológica , Biologia
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